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Mazhinji metabolic fundo mumakonzo anoitwa pamhepo tembiricha, kunyangwe ari mumamiriro ezvinhu aya, asingafananidzi vanhu, zvinongedzo zvinoshandiswa nesimba rakawanda kuchengetedza kupisa kwemukati. Pano, isu tinotsanangura zvakajairwa uremu uye kudya-kwekudya kwekudya (dio) muC57bl / 6j makonzo akadya chow kana 45% yakakwirira mafuta chikafu, zvichiteerana. Makonzo akaiswa kwemazuva makumi matatu nemasere aine 22, 25, 27.5 uye 30 ° C. Mune zvisina kunanga calarimetry system. Isu tinoratidza kuti mari yesimba inowedzera mutsara kubva pa30 ° C kusvika ku22 ° C uye iri anenge 30% yakakwira pa2 22 ° C mune ese mataira emamope. Mune yakajairika kurema makonzo, chikafu chekudya chinodzvinyirira ee. Kukurukurirana, Dio makonzo haana kuderedza kudya kwekudya kana ee yakaderera. Saka, pakupera kwechidzidzo, makonzo ari makumi matatu. Iko kusaenzana mu dio makonzo kunogona kunge kuri nekuda kwekuwedzera kwemafaro ekudya.
Iyo mbeva ndiyo inowanzo shandiswa mhando yemhuka yekudzidza kwevanhu phepfeliology uye pathophysiology, uye kazhinji mhuka yakasarudzika inoshandiswa mumatanho ekutanga ekuwanikwa kwezvinodhaka uye kukura. Nekudaro, makonzo anosiyana nevanhu munzira dzinoverengeka dzakakosha, uye nepo allometric scaling inogona kushandiswa kusvika padanho rekushandura muvanhu, mutsauko wakakura pakati pemakonzo uye vanhu vanonyepa muTermoregation uye Energy Homostasis. Izvi zvinoratidza kusapindirana kwakakosha. Avhareji yemuviri yemuviri yemakonzo anokwana koni kanokwana chiuru pane icho chevakuru (50 g vs.Goze kusvika pamakumi mashanu emakumi mana nekuda kweiyo isina-mutsara geometric transformation yakatsanangurwa neyeye . Equation 2. Nekuda kweizvozvo, makonzo anorasikirwa zvakanyanya nekupisa kwehuwandu kune vhoriyamu yavo, saka ivo vane hanya nekudziya, vanowedzera hypothermia, uye vane averal metabol rate kagumi kupfuura iyo yevanhu. Panguva yekudziya kwemimba (~ 22 ° C), makonzo anofanirwa kuwedzera yavo yakazara simba mashandisirwo (ee) ne30% kuchengetedza tembiricha yemuviri. Kumba kwakadzika, ee inowedzera zvakanyanya neanenge 50% uye 100% pa15 uye 7 ° C. ° C. Nokudaro, midzi yemimba yekugara ichinyengerera kushushikana kwekushushikana, iyo inogona kukanganisa kushamwaridzana kwembira tembiricha, sezvo isu tichigadzira iyo thermforral zone (tnz) yakatenderedza isu yakakwira uye yakatetepa bhendi inotanga chete 2 Gadzirira nekuwedzera kweshell tembiricha 9 Nekudaro, kungave kushoma kwezasi tembiricha mune iyo tembiricha mune yebenzi mumbiko imwe chete iri pedyo ne25 ° C) C4 ° C4, 7, 8, 10, 12 inoramba yakapokana. Ee uye mamwe metabolic paramita akaganhurirwa kwemaawa kusvika pamazuva, saka huwandu hwaifumurwa kwenguva refu kune dzakasiyana temberi dzinogona kukanganisa metampamita senge uremu hwemuviri hauna kujeka. Kutamisa, Substrate Kushandisa, Glucose Kushivirira, uye Plasma LIPID uye Glucose Kutarisisa uye Kuyera-Kurovera Mahormone. Uye zvakare Kuti tipe ruzivo rwakawanda pamusoro penyaya iyi, takaongorora mhedzisiro yekurera tembiricha pane zvataurwa metabeter mune yakajairika metamites Makonzo akaitirwa na22, 25, 27.5, kana makumi matatu ° C kweanenge vhiki nhatu. Tembiricha pazasi 22 ° C haisati dzadzidzwa nekuti standard mhuka dzimba dzisingawanzo zasi kwekamuri tembiricha. Takawana kuti zvakajairika-kurema uye single-circle dio makonzo akapindura nenzira yakafanana nekuchinja kwekushisa kwekushisa mumitemo Nekudaro, nepo zvakajairika kurema makonzo zvakachinjirwa kudya kwavo kwekudya maererano ne ee, chikafu chekudya chaDio chakazvimiririra cheEx, zvichikonzera zvinongedzo zvinowedzera uremu. Sekureva kwehuremu hwemuviri, plasma enjodzi dze lipids uye miviri yeketoni yakaratidza kuti dio makonzo pa30 ° C yaive neine simba rakanakisa pane mavara pa 22 ° C. Zvikonzero zvepasi pekusiyana mukusiyana kwekudya kwesimba uye ee pakati pehuremu hwakajairika uye dio mbeva dzinoda kuenderera mberi nekudzidzira,
Ee yakawedzera mutsara kubva pamakumi matatu kusvika ku22 ° C uye yaive anenge 30% yakakwira pa 22 ° C (Fig. 1a, b). Iyo yekufema yekuchinjana yekutsinhana (rer) yakazvimirira yekupisa (Fig. 1c, d). Kudya kwechikafu kwaive kuenderana neEE simba uye nekuwedzera nekudziya tembiricha (zvakare ~ ~ 1G). -To).
Makonzo echirume (C57bl / 6J Mazuva maviri mushure mekuunganidzwa kwedata rekumashure, tembiricha yakamutswa mu2 ° C.SH ZVAKAITWA PA 08:00 maawa pazuva (kutanga kwechikamu chechiedza). Dhata inoburitswa seyinoreva A Energy Internet (Zero kukosha inotsanangurwa se0.7). e cumulative chikafu chekudya (g) ). Iwo makonzo akachengetwa pakudziya kwakaratidzwa kwemaawa makumi mana nemasere. Data inoratidzwa ye 24, 26, 28 uye 30 ° C inoreva maawa makumi maviri nemana ekupedzisira ekutenderera kwega kwega. Makonzo akaramba agadyara munguva yese yekudzidza. Statistical kukosha yakaedzwa nekudzokorora zviyero zveimwe-nzira inovoteera neTukey's yakawanda kuenzanisa bvunzo bvunzo. Asterisks inoratidza kukosha kwekutanga kukosha kwe2 22 ° C, shading inoratidza kukosha pakati pemamwe mapoka sezvakaratidzwa. * P <0.05, ** P <0.01, ** P <0.001, **** p <0.0001. * P <0.05, ** P <0.01, ** P <0.001, **** p <0.0001. * P <0,05, ** P <0,01, ** P <0,001, **** p <0,0001. * P <0.05, ** P <0.01, ** P <0.001, **** p <0.0001. * P <0.05, ** P <0.01, ** P <0.001, **** p <0.0001. * P <0.05, ** P <0.01, ** P <0.001, **** p <0.0001. * P <0,05, ** P <0,01, ** P <0,001, **** p <0,0001. * P <0.05, ** P <0.01, ** P <0.001, **** p <0.0001.Avhareji tsika dzakaverengerwa kune iyo yose yekuedza nguva (0-192 maawa). n = 7.
Sezvineiwo mune yakajairika kurema makonzo, ee yakawedzera mutsara nekudzora tembiricha, uye mune ino kesi, ee yaive zvakare inenge 30% yakakwira pa2 22 ° C (fig. 2a, b). Rer haana kuchinja ongororo dzakasiyana (Fig. 2c, d). Mukupesana neyakajairwa uremu makonzo, chikafu chekudya hachina kuwirirana nee sebasa rekushisa kwemakamuri. Chikafu chekudya, kudya kwemvura, uye nhanho yekuita yakazvimirira yekupisa (maonde. 2e-j).
Male (C57BL / 6J Makonzo anogona kushandisa 45% HFD ad libitum. Mushure mekunge acclimatization kwemazuva maviri, baseline data yakaunganidzwa. Pashure pacho, tembiricha yakamutswa mukuwedzera kwe2 ° C mamwe ose zuva pa 06:00 (kutanga kweiyo cless chikamu). Dhata inoburitswa seyinoreva A Energy Internet (Zero kukosha inotsanangurwa se0.7). e cumulative chikafu chekudya (g) ). Iwo makonzo akachengetwa pakudziya kwakaratidzwa kwemaawa makumi mana nemasere. Data inoratidzwa ye 24, 26, 28 uye 30 ° C inoreva maawa makumi maviri nemana ekupedzisira ekutenderera kwega kwega. Makonzo akachengetedzwa pa45% HFD kusvika pakupera kwekudzidza. Statistical kukosha yakaedzwa nekudzokorora zviyero zveimwe-nzira inovoteera neTukey's yakawanda kuenzanisa bvunzo. Asterisks inoratidza kukosha kwekutanga kukosha kwe2 22 ° C, shading inoratidza kukosha pakati pemamwe mapoka sezvakaratidzwa. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * (0,05, *** (0,001, **** р <0,0001. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * (0,05, *** (0,001, **** р <0,0001. * P <0.05, *** p <0.001, **** p <0.0001.Avhareji tsika dzakaverengerwa kune iyo yose yekuedza nguva (0-192 maawa). n = 7.
Mune imwe nhevedzano yekuedza, takaongorora mhedzisiro ye ambient tembiricha pane iyo mapoka akafanana, asi panguva ino pakati pemapoka emakonzo ayo aigara achichengetwa pane imwe tembiricha. Makonzo akapatsanurwa kuita mapoka mana kuti aderedze shanduko dzehuwandu mune zvinoreva uye yakajairika kutsauka kwehuremu hwemuviri, mafuta, uye yakajairika muviri (2a-c). Mushure memazuva manomwe eAcclimatization, 4,5 mazuva eEe zvakanyorwa. Ee zvakakanganiswa zvakanyanya neyekushisa tembiricha ese panguva yemasikati uye manheru (fig. 3d) tembiricha inoderera kubva ku21 ° C (Fig. 3e). Kuenzaniswa nemamwe mapoka, Res yeiyo ° C GROUNT YAKAITWA, uye pakanga pasina misiyano pakati pemapoka akasara (Fig. 3F, G). Chikafu chekudya chakafanana neEE maitiro akawedzera neanenge 30% pa 22 ° C (fig. 3h, i). Mvura yekudhara uye zviyero zvezviitiko hazvina kusiyana zvakanyanya pakati pemapoka (Fig. 3j, k). Kuratidzwa kune tembiricha dzakasiyana siyana kusvika pamazuva makumi matatu nematanhatu haina kutungamira mukusiyana muhuremu hwemuviri, uye yakafa misa pakati pemapoka (Fat. 3n-s), kuzvitaura kuzvitaura zviyero (Fig. 3n-s). 3b, r, c) uye mafuta akawedzera neanopfuura 2 times (kubva ~ 1 g kusvika 2-3 g, fig. 3c, t, c). Nehurombo, iyo 30 ° C cabinet ine calibration zvikanganiso uye haigone kupa chaiyo ee uye reer data.
- uremu hwemuviri (a), lean misa (b) uye mafuta masasi (c) mushure memazuva masere (rimwe zuva usati waendesa kune system system). D Simba rekushandisa (kcal / h). E averal esimba rekushandisa (0-108 maawa) pakudziya kwakasiyana-siyana (KCAL / maawa makumi maviri nemana). F yekufema yekuchinjana ratio (rer) (VCO2 / VO2). g zvinoreva rer (VCO2 / VO2). H Azere chikafu chekudya (g). Ndinoreva chikafu chekudya (g / maawa makumi maviri nemana). j yakazara mvura yekudhara (ML). Kavhareji yemvura yekudyara (ml / 24 h). l cumulative chiitiko chechiitiko (m). mavhareji chiitiko chezviitiko (m / 24 h). n Muviri uremu pazuva regumi nemasere, o Shanduko muhuremu hwemuviri (kubva -8 kusvika paZuva regumi nemasere, , uye shanduko mumafuta mafuta (kubva -8 kusvika pamazuva gumi nemasere). Iko kukosha kwehuwandu kwekudzokororwa kuyerwa kwakaedzwa neAneway-anova inoteverwa neTukey's yakawanda kuenzanisa bvunzo. * P <0.05, ** P <0.01, *** P <0.001, **** p <0.0001. * P <0.05, ** P <0.01, *** P <0.001, **** p <0.0001. * P <0,05, ** P <0,01, *** P <0,001, **** p <0,0001. * P <0.05, ** P <0.01, *** P <0.001, **** p <0.0001. * P <0.05, ** P <0.01, *** P <0.001, **** p <0.0001. * P <0.05, ** P <0.01, *** P <0.001, **** p <0.0001. * P <0,05, ** P <0,01, *** P <0,001, **** p <0,0001. * P <0.05, ** P <0.01, *** P <0.001, **** p <0.0001.Dhata inoburitswa seyisingarevi + yakakanganisika kukanganisa kweizvozvo, iyo dema chikamu (18: 00-06: 00 h) inomiririrwa nemabhokisi egrey. Madhiri pamakonzo anomiririra manyadzi. Avhareji tsika dzakaverengerwa nguva yese yekuedza yekuedza (0-108 maawa). n = 7.
Makonzo aiverengerwa mumuviri, lean misa, uye mafuta masvomhu paBaseline (maonde. 4a-c) uye anochengetwa na25, 25, 27,5, uye 30 ° C se muzvidzidzo zvine huremu hwakajairwa. . Paunenge uchienzanisa mapoka emakonzo, hukama pakati peEe uye tembiricha zvakaratidza zvakafanana mutsara hukama nekushisa nekufamba kwenguva mumakonzo akafanana. Nekudaro, makonzo anochengetwa na2 22 ° C anotyiwa anenge 30% simba kupfuura makonzo anochengetwa makumi matatu nemashanu C (Fig. 4d, e). Kana kudzidza mhedzisiro mumhuka, tembiricha haina kugara ichikanganisa reer (Fig. 4f, g). Chikafu chekudya, kudya kwemvura, uye chiitiko hachina kukanganiswa zvakanyanya nekushisa (maonde. 4H-m). Mushure memazuva makumi matatu nematanhatu ekurera, makonzo ari makumi matatu Kuenzaniswa nenongedzo yavo yeBaseline, makonzo akarariswa pa30 ° C aive nehuwandu hwepamusoro hwemuviri pane makonzo akarererwa pa 22 ° C (zvinoreva ± yakajairika kukanganisa kweiyo zvinoreva: Fig. 4o). Iyo yakakwira yakakura kuwana yaive nekuda kwekuwedzera kwemafuta misa (fig. 4p, q) pane kuwedzera kuwanda (fig. 4r. Inowirirana neyekupedzisira ee kukosha pagumi nemashanu C. ° C, kuratidzwa kwematanho akati wandei anowedzera bat basa / basa rakaderedzwa kusvika makumi maviri. Mamwe majini akakosha anowedzerawo bat basa / basa haana kukanganiswa: Sema3a Zvinoshamisa kuti, UCP1 uye vegf-a, inosanganiswa neyakawedzera chiitiko cheTromogenic, haina kuderera muboka ramakumi matatu. Muchokwadi, mazinga eUCP Kuenzaniswa neAI ° C Boka, Makonzo akachengetwa pa25 ° C uye 27.5 ° C yakaratidza hapana shanduko (Supplementary Mufananidzo 1).
- uremu hwemuviri (a), lean misa (b) uye mafuta masasi (c) mushure memazuva makumi mapfumbamwe (rimwe zuva usati waendesa kune system system). D simba rekushandisa (ee, kcal / h). E average avhareji yekushandisa (0-96 maawa) pakudziya kwakasiyana-siyana (KCAL / maawa makumi maviri nemana). F yekufema yekuchinjana ratio (rer, vco2 / vo2). g zvinoreva rer (VCO2 / VO2). H Azere chikafu chekudya (g). Ndinoreva chikafu chekudya (g / maawa makumi maviri nemana). j yakazara mvura yekudhara (ML). Kavhareji yemvura yekudyara (ml / 24 h). l cumulative chiitiko chechiitiko (m). mavhareji chiitiko chezviitiko (m / 24 h). n Muviri uremu pazuva 23 (g), o shanduko muhuremu hwemuviri, P LEAN MAST, Misa (g) ichienzaniswa nezuva 8, zuva 23 tichienzanisa ne -8th zuva. Iko kukosha kwehuwandu kwekudzokororwa kuyerwa kwakaedzwa neAneway-anova inoteverwa neTukey's yakawanda kuenzanisa bvunzo. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * (0,05, *** (0,001, **** р <0,0001. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * (0,05, *** (0,001, **** р <0,0001. * P <0.05, *** p <0.001, **** p <0.0001.Dhata inoburitswa seyisingarevi + yakakanganisika kukanganisa kweizvozvo, iyo dema chikamu (18: 00-06: 00 h) inomiririrwa nemabhokisi egrey. Madhiri pamakonzo anomiririra manyadzi. Zvinoreva kukosha kwakaverengerwa nguva yese yekuedza (0-96 maawa). n = 7.
Kufanana nevanhu, makonzo anowanzogadzira microenvironments microenvonments kuderedza kupisa kupisa kune nharaunda. Kuti tisiyane kukosha kwenzvimbo iyi yeEE, taiongorora ee naEe, 25, 27.5, uye 30 c, ine kana isina vatariri vematehwe uye nesting. Pa 22 ° C, kuwedzera kweiyo standard matehwe kunodzora ee ne4%. Kuwedzeredzwa kwakazotevera kwekurongedza zvinhu kwakaderedza ee na3-4% (Fig. 5a, b). Hapana shanduko dzakakosha muRer, kudya kwechikafu, kudya kwemvura, kana zviyero zvekuita zvakaonekwa nekuwedzera kwedzimba kana mabheji + ematehwe (Mufananidzo 5I-p). Kuwedzera kweganda uye nesting zvinhu zvakare kwakaderedzwa pamwe chete ne25 kusvika makumi matatu ° C, asi mhinduro dzaive diki diki. Na 27.5 ° C hapana mutsauko wacho wakacherechedzwa. Zvakare, mune izvi kuedza, ee akaderera nekuwedzera kupisa, mune ino nyaya anenge 57% yakaderera pane ee pa3 ° C (fig. 5c-h). Kuongorora kumwechete kwakaitwa chete kune iyo chete yechiedza chikamu, uko iyo iyo ee yaive pedyo neiyo basal metabolic chiyero, zvichikonzera kuenzanisa maitiro kune akasiyana tembiricha (Supplementary fig. 2a-h) .
Dhata yemakonzo kubva pakugara uye nesting zvinhu (yakasviba yebhuruu), imba asi isina-esting zvinhu (mwenje yebhuruu), uye nedendere uye dendere). Simba rekushandisa (ee, kcal / h) yemakamuri a, c, e uye g kuma 22, 25, 27.5 uye 30 ° C, b, d, f uye h nzira (kcal / h). Ip data yemakonzo akaiswa pa12 ° C: Ini rer, Vco2 / VO2), VCO2 / G / G / G / G / M Yese yekudya kwemvura (ML), N Avhareji Wemvura Incoake Auc (ML / 24h), o Yese Chiitiko (M), P Avhareji Yekuita Chikamu (M / 24H). Dhata inoburitswa seyisingarevi + yakakanganisika kukanganisa kweizvozvo, iyo dema chikamu (18: 00-06: 00 h) inomiririrwa nemabhokisi egrey. Madhiri pamakonzo anomiririra manyadzi. Iko kukosha kwehuwandu kwekudzokororwa kuyerwa kwakaedzwa neAneway-anova inoteverwa neTukey's yakawanda kuenzanisa bvunzo. * P <0.05, ** P <0.01. * P <0.05, ** P <0.01. * (0,05, ** р <0,01. * P <0.05, ** P <0.01. * P <0.05, ** P <0.01. * P <0.05, ** P <0.01. * (0,05, ** р <0,01. * P <0.05, ** P <0.01.Avhareji tsika dzakaverengerwa kune iyo yose yekuedza nguva (0-72 maawa). n = 7.
Mune zvakajairika kuremerwa makonzo (maawa 2-3 ekutsanya), kurera tembiricha dzakasiyana siyana hakuna kuguma nekusiyana kwakakosha muPlasma kutarisisa kweTG, 3-HB, cholesterol, Alt, asi HDL sebasa rekushisa. Mufananidzo 6A-E). Kutsanya plasma ongororo ye leptin, insulin, c-peptide, uye glucagon zvakare haina kusiyana pakati pemapoka (manhamba 6g-j). Pazuva reGlucose Testance Test (mushure memazuva 31 pane dzakasiyana tembiricha), iyo Baseline Ropa Glucose Level (5-6 maawa ekutsanya) waive anenge 6.5 mm, pasina mutsauko pakati pemapoka. Manejimendi eOral Glucose yakawedzera kutarisisa kweropa zvakanyanya mumapoka ese, asi zvese zvepamusoro nzvimbo pasi peboka remucheka <0.05-p <0.0001, fig. 6k, l) achienzaniswa nemakonzo akagara pa22, 25 ne 27.5 ° C (izvo zvisina kusiyana pakati peumwe neumwe zvimwe). Manejimendi eOral Glucose yakawedzera kutarisisa kweropa zvakanyanya mumapoka ese, asi zvese zvepamusoro nzvimbo pasi peboka remucheka <0.05-p <0.0001, fig. 6k, l) uchienzaniswa nemakonzo akagara pa22, 25 ne 27.5 ° C (iyo isina kusiyana pakati peumwe neumwe zvimwe). Пероральное введение гюкозы вовыш ко ли Прод од о (15-12 еин) былиржихся при 30 ° C (отдельные ве 6k, l) по с равнению, одержащимися при 2, 25 ° 22 ° C (W5 27 ° C (V)). Muromo wekutonga kweGlucose zvakanyanya kuwedzera kweropa P <0.0001, fig. 6k, l) uchienzaniswa nemakonzo anochengetwa na22, 25 ne 27.5 ° C (iyo isina kusiyana kubva kune mumwe nemumwe).口服葡萄糖的给药显着增加了所有组的血糖浓度, ° C 饲养的小鼠组中, 峰值浓度和曲线下增加面积 (iauc) (15-120 分钟) 均较低 (各个时间点: P <0.05-p <0.0001,】 6k, l) 与饲养在 22,25 和 27.5 ° C 的小鼠 (°) 相比.口服 葡萄糖 的 给 药 所有组 所有组 的 在 在 在 在 在, (15-12) (15-120 分钟) (15-120 分钟) (15-120) (15-120 分钟)点 点: P <0.05-p < 0.0001,】 6k, l) 与饲养在 22,25 和 27.5 ° C 的小鼠 (彼此之间没有差异) 相比.Oral Administration yeGlucose yakanyanya kuwedzera nzvimbo yeropa mumapoka ese, asi zvese zvepamusoro zvekusangana uye nharaunda yepasi pevhu (auc) (15-120 min) yaive yakaderera muboka remakumi matatu.: P <0,05-p <0,0001, рис. : P <0.05-p <0.0001, Fi.6l, l) tichienzanisa neakanaka zvakachengetwa na12, 25 uye 27.5 ° C (hapana mutsauko kubva kune mumwe nemumwe).
Plasma ongororo yeTG, 3-HB, Cholesterol, Hdl, Altr, Astrol, Luptin, Insulin, Insopt . Makonzo haana kugutswa maawa 2-3 maawa pamberi peropa. Kusarudzika kwaive muedzo wemuromo wekushivirira, iyo yakaitwa mazuva maviri ekupedzisira ekudzidza pamakonzo akatsemuka kwemaawa 5-6 uye anochengeterwa tembiricha yakakodzera kwemazuva 31. Makonzo akapokana ne 2 g / kg muviri uremu. Iyo nharaunda iri pasi peiyo curve data (l) inoratidzwa se data rinowedzera (IAUC). Dhata inoburitswa seye zvinoreva ± SEM. Madhiri anomiririra samples imwe chete. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0,05, ** P <0,01, ** P <0,001, **** P <0,0001, n = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0,05, ** P <0,01, ** P <0,001, **** P <0,0001, n = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7.
MuDio makonzo (akamhanyawo kwemaawa 2-3), plasma cholesterol, Hdl, Alt, AST, uye FFAntirations haina kusiyana pakati pemapoka ari pakati pemapoka. TG zvese uye glycerol yaive yakakwidziridzwa zvakanyanya mune makumi matatu ° C iboka zvichienzaniswa ne12 ° C GROUNT (NYAYA 7A-H). Mukupesana, 3-GB yaive anenge 25% yakaderera pa30 ° C Aenzaniswa kusvika pa2 22 ° C (Mufananidzo 7b). Nekudaro, kunyangwe mbeva ichengetwe pa 22 ° C yaive neyakazara simba simba chiyero, sezvakakurudzirwa nehuremu hwekuita tg, glycerocarations ye tg, glycrol, uye 3-hb inopa kuti mbeva pa 22 ° C kana sampling yaive isingasviki 22 ° C. ° C. Makonzo akararazve pa30 ° C aive mune imwe nzvimbo ine simba risina kunaka. Inowirirana neiyi, chiropa chemafuta eglycerable glycract uye tg, asi kwete glycogen uye cholesterol, yaive yakakwira muboka ramakumi matatu Kuti uongorore kana kusiyana-tembiricha kusiyana (sekuyerwa nePlasma tg uye glycrol) mitezo kubva kune izvi zvitoro pakupera kwekudzidza uye kuwanda kwemahara mafuta acid exid ex vivo. uye kusunungurwa kweGlycerol. Mumapoka ese ekuedza, anoshongedza samples kubva kune Epidiym uye Inguinal Depots kuwanda kweGycerol uye FAFA DEAPROTENTOL kukurudzira (Supplementary fig. 4a-d). Nekudaro, hapana mhedzisiro yekushisa kweshell pane yebasa kana istoproterenol-yakakurudzirwa lipolis yakawanikwa. Inowirirana nehuremu hwemuviri uye hwakawanda hwehuremu, plasma leptin mazinga akanyanya kukwirisa muboka makumi matatu ° C Boka pane muboka ra2 22 ° C Boka (Mufananidzo 7I). Pane zvinopesana, mazinga eplasma e insulin uye cptide haana kusiyana pakati pekudziya mapoka (Fig. kusvika pamakumi matatu. Kubva. Boka c (fig. 7l). FGF21 haina kusiyana pakati pemapoka ekudziya akasiyana (Fig. 7m). Pazuva reOgt, Baseline Ropa Glucose raive anenge gumi mm uye haana kusiyana pakati pemakonzo akaiswa munzvimbo dzakasiyana (Fig. 7n). Oral Administration yeGlucose yakawedzera log glucose mazinga uye yakakwira mumapoka ese pakusangana kweanenge 18 mm maminitsi mushure mekurasa. Pakanga pasina mutsauko wakakosha muIAUC (15-120 min) uye kutarisisa panguva dzakasiyana nguva mapoinzi post-doseti (15, 60, 90 min) (Mufananidzo 70, O).
Plasma ongororo yeTG, 3--cholesterol, Hdl, Alt, FFELT, Insulin, GLCUGON, AOO) Makonzo Akuru (AO) Makonzo Mushure memazuva makumi matatu ekudyira. tembiricha yakatsanangurwa. Makonzo haana kugutswa maawa 2-3 maawa pamberi peropa. Iyo yemuromo yedlucose yekushivirira testance yaive kunze kweiyo yakaitwa paDook ye2 G / KG muviri uremu mazuva maviri usati wapera kwemaawa mashanu uye uchichengetwa pakupisa kwemazuva makumi matatu nemasere. Iyo nharaunda iri pasi peiyo curve data (o) inoratidzwa se data rinowedzera (IAUC). Dhata inoburitswa seye zvinoreva ± SEM. Madhiri anomiririra samples imwe chete. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0,05, ** P <0,01, ** P <0,001, **** P <0,0001, n = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7. * P <0,05, ** P <0,01, ** P <0,001, **** P <0,0001, n = 7. * P <0.05, ** P <0.01, ** P <0.001, **** P <0.0001, N = 7.
Iko kutengeswa kwetsiva data kuvanhu inyaya yakaoma iyo inoita basa repakati mukududzira kukosha kwekucherechedzwa mumamiriro ezvinyorwa zvehupamhi uye pharmacological kutsvagurudza. Nezvikonzero zvehupfumi uye kufambisa kutsvagisa, makonzo anowanzochengetwa pamhepo tembiricha pazasi penzvimbo yavo yemuviri, inokonzerwa nekurovedza muviri kwakasiyana-siyana kunowedzera iyo metabolic chiyero uye inogona kukanganisa kudzora kwetrate9. Nekudaro, kuratidzwa kwemakonzo kune chando kunogona kupa mbeva kunodzivirira kwekudya-kwekudya uye kunogona kudzivirira hypergotocemia muRedPotopotecomia-yakarapwa makonzo nekuda kwekuwedzera kusiri-insulin Nekudaro, hazvisi pachena kuti ndeipi nguva refu yekuregererwa kune dzakasiyana tembiricha (kubva kuimba yekudhinda) inokanganisa iyo yakasiyana simba remba yehuremu Kwavakagona kuyera kuwedzera kweEe nekuwedzera kwekudya kwekudya. Chidzidzo chakaratidzwa muchinyorwa chino chinotarisira kuunza kujekesa kune iyi nyaya.
Isu tinoratidza kuti mune yakajairika yakaremerwa mbeva uye murume wechirume dio, ee inoenderana neyakawirirana nemhepo tembiricha pakati pegumi nemakumi matatu nemakumi matatu c. Saka, ee pa 22 ° C yaive anenge 30% yakakwirira kupfuura makumi matatu c. mune zvese zvombo mhezi. Nekudaro, musiyano wakakosha pakati pehuremu hwakajairika uye dio mbeva ndezvekuti nepo zvakajairika kurema makonzo zvakakwenenzverwa nekugadzirisa chikafu, chikafu cheDio monice akasiyana pamatanho akasiyana. Kupisa kwekudzidza kwakafanana. Mushure memwedzi mumwe, Dio makonzo akachengetwa pa30 ° CLEED YAKABUDA MUMUMAI WEMUKADZI NEZVINHU ZVAKAITWA PAKUTI SEI CLASTY TIMBASE uye nguva imwe chete yenguva haina kutungamira kufivha. kutsamira mutsauko mu uremu hwemuviri. kurema makonzo. Kuenzaniswa nekudziya padyo nedhorobha rekutenderera kana kumhepo tembiricha, kukura kwemakamuri kwakakonzera dio kana zvakajairika kuremerwa kwemafuta ekudya asi kune yakajairika hope kuti uwane uremu hushoma. muviri. Yakatsigirwa nezvimwe zvidzidzo17,18,19,20,21 asi kwete nevose22,23.
Iko kugona kugadzira microenvongement kuti uderedze kurasikirwa kwekushisa ndeye hypothesized yekuchinja kusarerekera kusara kusvika kuruboshwe8, 12. Mukudzidza kwedu, kuvanda kwakaderedza kusapindira kusarerekera kusvika 28 ° C. Saka, data redu haribvumirane kuti iyo yakaderera pfungwa yekufambisa mumbiko dzemberi, kana pasina dzimba dzakatipoteredza, dzinofanira kutsigira zvimwe zvidzidzo zvinoratidza kufambidzana. tembiricha yegumi nemakumi matatu ° C low Point Kirion: 10, 24. Kuomesa zvinhu mumakonzo akanzi asationgororwe panguva yekuzorora (yechiedza) chikamu chezasi kugadzirwa semhedzisiro yebasa uye kudya-kunyengedzwa thermenziis. Nekudaro, muchikamu chechiedza, iyo yepazasi point yekuisa kusarerekera kunochinja kuva ~ 29 ° °,, uye mune dema phare, ° ° с25.
Pakupedzisira, hukama pakati peAmerient tembiricha uye huwandu hwesimba hwekushandisa hunotemwa nekupisa kusarongeka. Mundima iyi, huwandu hwenzvimbo yemusoro kune vhoriyamu ndeyekukosha kwakakosha kwekunzwa kwekunzwa kwekunyora Kuwedzera kune nzvimbo yemusoro, kupisa kupisa kwakatsemurwa neisimbichi (chiyero chekushisa kupisa). Muvanhu, misa yakakora inogona kuderedza kupisa kwekupisa nekugadzira chipinganidzo chakakanganisika. Uye zvakaratidzwa kuti mafuta akakosha kuti awedzere kufambisa curve inotsvedza). ambient tembiricha ichienzaniswa neEE) 12. Kudzidza kwedu hakuna kugadzirwa kuti uongorore zvakananga hukama uhu nekuti data yemuviri yakaunganidzwa mazuva 9 isati yaunganidzwa data uye nekuti misa yakakora haina kugadzikana munguva yese yekudzidza. Nekudaro, sezvo yakajairwa uremu uye dio makonzo ane 30% yakaderera ee pa3 ° C pane pane imwe chete mutsauko we5-fodya mudenga chinhu, zvirinani kwete mune yakadzama tembiricha yekupisa. Izvi zvinoenderana nezvimwe zvidzidzo zvakagadzirirwa kuongorora izvi4,24. Muzvidzidzo izvi, mhedzisiro yekufutisa yekufutisa yaive diki, asi fur yakawanikwa ichipa 30-50% yehuwandu hwekuparadza kweintsulation4,24. Nekudaro, mumakonzo akafa, mafambiro akafa akawedzera kusvika pa450% pakarepo mushure mekufa, achiratidza kuti kusimbisa kwemba kunodiwa kune michina yemuviri, kusanganisira kusimudzira kusarudzika, kushanda. Kuwedzera kune mhando misiyano mufuro pakati pemakonzo uye vanhu, iyo isingafadzi yekufutisa nekufunga kwemurume anotevera: Chinyorwa cheMafuta chevanhu chinonyanya kufambiswa nemakungwa ega Kazhinji mumakonzo zvisingasviki 20% yehuwandu hwemhuka hwakazara makumi maviri. Uye zvakare, yakazara mafuta marudzi anogona kunge asingambove muyero wechiSubeptimal nezvekunzwa kwemunhu, sezvo zvakakanganiswa neyakawedzera kuwanda kwenzvimbo yekuwedzera (uye nekudaro yakawedzera kurasikirwa) sekuwedzera kwemafuta kunowedzera. .
Mune zvakajairika kuremerwa makonzo, kutsanya plasma kutarisisa kwe tg, 3--cholesterol, Hdl, Altl, Alt, Alt, Alt, Alt, Alt, Alt vaive zvakafanana muhuremu uye kuumbwa kwemuviri sekupera kwechidzidzo. Zvinoenderana neyakafanana nemisa mafuta, pakanga pasina misiyano muPlasma Leptin mazinga, kana insulin, C-Peptide, uye Glucagon. Mimwe masaini akawanikwa mu dio makonzo. Kunyangwe makonzo pa 22 ° CLEARY YAKAITWA YAKAITWA SIMBA BHUKU MUZVINHU ZVAKAWANDA (Sezvo ivo vakawana huremu), pakupera kwesimba ravanga vari kusakwana vachienzaniswa nemakonzo ari pa30 ° C, mune mamiriro akadai se yakakwirira ketoni. kugadzirwa nemuviri (3-gb) uye kuderera mukusangana kweGlycel uye tg muPlasma. Nekudaro, tembiricha-inovimbika misiyano muLipolyssis haina kuratidzika kunge ichishanduka mapoka akafanana neumwe neumwe. Kunyangwe isu tisina kuongorora tarisiro inonzwira tsitsi mune ikozvino kudzidza, vamwe vakaona kuti iyo (yakavakirwa pamwoyo mhanya) inoenderana neyemukati medanho mune makumi matatu ° C pane pane 22 ° C 20% C Saka, tembiricha-inovimbika misiyano mukunzwira tsitsi toni inogona kutamba chiitiko muLipolysis mukudzidza kwedu, asi sezvo kuwedzera kunzwira tsitsi toni kunonzwira tsitsi kwete inhibits Lipolysis, mamwe mashini anogona kurwisa izvi kuderera mumakonzo echikamu. Basa racho rinogona kuitika mukuparara kwemafuta emuviri. Kupisa kwemakamuri. Uyezve, chikamu chekusimudzira mhedzisiro yemanzwiro anonzwira tsitsi pamusoro pekunzwa zvisina kufanira neInsulin Clubon isina kukwana kushandura lifolysis. Panzvimbo pezvo, takaona kuti misiyano iri mune simba mamiriro kazhinji ingangove iyo huru inobatsira kune aya misiyano mu dio makonzo. Zvikonzero zvepasi pekutanga zvinotungamira kune zviri nani mutemo wekudya kwekudya zvine ee mune zvakajairika uremu zvibodzwa zvinoda kuenderera mberi nekudzidza. Muzhinji, zvakadaro, kudya kwechikafu kunodzorwa nePamba uye Hedonic Cues31,32,33. Kunyangwe paine nharo kuti ndeipi yezvikwangwani zvizhinji zvakanyanya, Homeostasis. . -Akadzora chikafu Chekudya34,36,36. Naizvozvo, iyo yakawedzera hedonic yekudyisa maitiro aDio makonzo akaratidzirwa ne45% HFD inogona kunge iri chimwe chezvikonzero nei aya makonzo asina kuyera chikafu chekudya chine ee. Sezvineiwo, kusiyana kwekudya uye kweropa glucose-kuoraira mahormone akaonekwawo mune tembiricha-inodzorwa dio dio, asi kwete yakajairika-yehuremu. MuDio Makonzo, Plasma Leptin mazinga akawedzera ne tembiricha uye glucaggon zviyero zvakadzikira nekudziya tembiricha. Sangano ripi raunogona kupisa zvakanyanya zvakananga misiyano dzakafanirwa nekuwedzera kudzidza, asi mune imwe nzvimbo isina kunaka semafuta muzvikamu 22 zvakanyanyisa corrated37. Nekudaro, kududzirwa kwesangano reGlucagon chiratidzo chinonyanya kushungurudza. Sezvineiwo neInNyin, Glucagon Seccion yakakanganiswa nekuwedzera munyoro, asi iyo toni yepamusoro yekunzwira tsitsi yakafanotaurwa kuti ive muboka ra2 22, iro rakanga riine plasma yakakwira glucagagon. Insulin ndeimwezve mugadziri akasimba wePlasma Glucaggon, uye insulin kuramba uye mhando 2 chirwere cheshuga chakabatana zvakanyanya nekutsanya uye postplandial hyperglonemia 38,39. Nekudaro, mbeva yaDio mukudzidza kwedu yaivewo insulin isingateereri, saka izvi zvakare hazvingadaro chinhu chikuru mukuwedzera kweGlucagon chiratidzo muboka raGucha reGuzi. Zvemukati zvechiropa zvine musoro zvakare zvakabatana nekuwedzera kweplasma glucagagon. 42. Nekudaro, sezvo ongororo dzinowedzera dzeGlycoratil uye tg haina kusiyana mapoka ekudziya mukudzidza kwedu, izvi zvakare hazvingagone kuve chinhu chinogona kuitika mukuwedzera kweplasma ivhu muboka ra2 22 ° C BGRENT. TrioDothyronine (T3) inotamba chinzvimbo chakakosha muhuwandu hwekuita metabolic uye kutanga kwe metabolic kudzivirira kubva kuHypothermia43,44. Saka, Plasma T3 Kusvirwa Izvi zvinowirirana nekurasikirwa kwekupisa kune nharaunda. Isu hatina kuyera plasma t3 pakudzidza kwazvino, asi zvingave zvakadzika muboka regumi neboka iri paPlasma Glucagon Glucagag Glucaggon, apo T3 inowedzera plasma glucagon mune dosi-inoenderana nenzira. Thyroid hormone yakataurwa kuti inyore yekufungidzira fgf21 kutaura mune chiropa. SaGlucagon, Plasma Fgf21 makomendi akawedzerawo nePlasma T3 Constarations (Supplementary Fig. 5b na Ref. 48), FGF21 plasma kutarisisa midziyo yedu haina kukanganiswa nekushisa. Zvikonzero zvepasi pekusiyana kweiyi musiyano unoda kuenderera mberi nekudzidza, asi T3-inotungamirwa fgf21 inction inofanirwa kuitika pamatanho eT3 kuenzaniswa kweT3-inotungamirwa Glucagon Mhinduro (Supplementary Fig. 5B).
HFD yakaratidzwa kuti isimbiswe zvakanyanya neisina kurwadza glucelance yekushivirira uye insulin kuramba (mamaki) mumakonzo akarerwa pa 22 ° C. Nekudaro, HFD haina kubatana neyakaverengerwa nehurongwa hweglucese yekushivirira kana insulin kuramba pakakura munzvimbo yedhiramu (inotsanangurwa pano se 28 ° C) 19. Mukudzidza kwedu, hukama uhwu hwainge husina kudzokororwa muDio makonzo, asi zvakajairika kuremerwa makonzo vakachengetedzwa pa30 ° C zvakanyanya kuvandudzwa kugadzikana kweglucose. Chikonzero chekusiyana kwemisiyano chinoda kuti uwedzere kudzidza, asi zvinogona kunge zvichikanganiswa nenyaya yekuti dio dio mukudzidza kwedu yaive insulin c-plasma c-inslin yekunzwa 12-16 nguva yakakwirira kupfuura yakajairika. uye muropa padumbu risina chinhu. Glucose kutarisisa kwe10 mm (anenge 6 mm kujairika muviri uremu), zvinoita kunge kusiya hwindo rakanaka kune chero mukana wekubatsira mukuratidzwa kwemamiriro ekunyora glucose kushivirira kweglucose. Chinhu chinogona kuitika chinovhiringidza ndechekuti, nekuda kwezvikonzero zvinoshanda, Ogtt inoitwa kumhepo tembiricha. Nekudaro, makonzo anogara achiomeswa tembiricha akasangana nedambudziko kutonhora kutonhora, izvo zvinogona kukanganisa glucose kusimuka / clearance. Nekudaro, zvichibva pane dzakafanana dzakatsamwisa dzakatarisana nemapoka ekudziya akasiyana, shanduko mune amburist tembiricha inogona kunge isina kunyanya kukanganisa mibairo.
Sezvambotaurwa, zvichangobva kuratidzwa kuti kuwedzera tembiricha yemakamuri kunogona kurongedza mamwe maitiro pakutonhora, izvo zvinogona kufona kuchibvunza kuti kutengeswa kwe data re mbeva. Nekudaro, hazvisi pachena kuti ndeipi tembiricha yekudziya yekuchengeta makonzo kune kutevedzera phyitiology yemunhu. Mhinduro kumubvunzo uyu inogona zvakare kukurudzirwa nemunda wekudzidza uye mhedzisiro ichidzidzwa. Muenzaniso weizvi ndiwo mhedzisiro yekudya pane chiropa mafuta kuwanda, glucose kutsungirira uye insulin kuramba19. Panyaya yeshandisirwo esimba, vamwe vanotsvaga vanotenda kuti tembiricha tembiricha yekuregedza, sezvo vanhu vanowedzera kupisa kwemuviri, uye vanotsanangura tembiricha yemumuviri, Vamwe vaongorori vanotenda kuti tembiricha yakafanana neiyo vanhu vanowanzoona nebvi revanhu vane makore makumi maviri nemasere yavo yakadzika yakaoma tembiricha, inotsanangurwa pano se 23 ° C, iri zvishoma 8.12. Kudzidza kwedu kunowirirana nezvimwe zvidzidzo zvinoverengeka kuti kusarerekera kunoitwa nevarerekesa vasingawanikwe pana 26-28 ° C4, 7, 10, 11, 24, 25, zvichiratidza kuti 23-25 ° C yakaderera. Chimwe chinhu chakakosha kufunga nezve nezve tembiricha yemakamuri uye kujaira mumakonzo mune imwe kana dzimba dzeboka. Kana makonzo akaiswa mumapoka pane mumwe nemumwe, sekudzidza kwedu, tembiricha yekudziya yakaderedzwa, pamwe nekuda kwekutsvagira mhuka. Nekudaro, tembiricha yemakamuri yakanga ichiri pazasi peLTL ye25 apo mapoka matatu akashandiswa. Zvichida inonyanya kukosha interspecial musiyano mune izvi kukosha kweiyo kukosha kweiyo bat chiitiko sekudzivirira kweHypothermia. Saka, nepo mbeva zvakanyatsogadzirirwa yavo yekukwira calorie kurasikirwa chiitiko, iyo inopfuura 60% ee pa 5 ° C ndega, Naizvozvo, kudzora chibharo chiitiko kunogona kunge kuri nzira yakakosha yekuwedzera kushandura kwevanhu. The regulation of BAT activity is complex but is often mediated by the combined effects of adrenergic stimulation, thyroid hormones and UCP114,54,55,56,57 expression. Yedu data inoratidza kuti tembiricha inoda kukwidziridzwa pamusoro 27.5 ° C.5 ° CEACE PAKUTI 22 ° C kuitira kuti uone mutsauko wekuratidzira kwesangano Nekudaro, misiyano yakawanikwa pakati pemapoka pa30 ne22 ° C haina kugara ichiratidza chiitiko muBat Boka servie Iyo inokonzeresa mhedzisiro yeiyi mhedzisiro isingatarisirwi inoramba ichitsanangurwa. Mumwe mukana ndewekuti kwavo kuratidzira kungasaratidzira chiratidzo chemakwikwi ekumhepo tembiricha, asi zviri nani zvinowedzera zvekusimudzira kubva pamakumi matatu. . ).
Kuganhurirwa kwakawanda kwekudzidza kwedu ndekwekuti isu takangodzidza makonzo echirume. Kumwe kutsvagisa kunoratidza kuti kukosheswa kunogona kuve kwekukosha kwezvedu zvinangwa zvedu, sekombi yembereko yechikadzi ndeyekuti tembiricha yekudziya yekuisa uye kuchengetedza kwakanyanya kudzora tembiricha. Mukuwedzera, mbeva yemukadzi (paHFD) yakaratidza kushamwaridzana kwakakura kwesimba kudya kweEE pa 30 ° C. Saka, mumakonzo echikadzi, maitiro ezvinyorwa zvechikadzi zvakakwira, asi ane maitiro akafanana akafanana nemakonzo echirume. Mukudzidza kwedu, takatarisa pane imwe chete-pfumo murume kana aya ndiwo mamiriro ezvinhu pasi pekuti metabolic ongororo yekuongorora ee anoitiswa. Kumwe kusiana kwekudzidza kwedu kwaive kwekudya kwakafanana kwekudzidza mukati mechidzidzo chemuchidzidzo chemuviri, sekuyerwa kweRer shanduko yekudya mune dzakasiyana siyana macronutrient yekuumbwa.. Mumakadzi uye mukonzo makonzo akachengetwa pa20 ° C ACCEKWA KUTI ANOGONESESESA ZVINOGONESESWA ANOGADZWA PAZUVA 30 CI C.
Mukupedzisa, kudzidza kwedu kunoratidza kuti, sekumikidzwa kwezvimwe zvidzidzo, pamakumbo 1 zvakajairwa uremu makonzo ari pamusoro peanofungidzirwa pamusoro pevane 27.5 ° C. Uye zvakare, kudzidza kwedu kunoratidza kuti kufutisa hachisi chinhu chikuru chokusimbisa mumakonzo nehuremu hwakajairika kana dio, zvichikonzera kupisa kwakafanana. Nepo chikafu chekudya chehuremu hwakajairwa chakaremerwa neee uye nekudaro vakachengeta huremu hwakagadzikana hwemuviri pamusoro pekudziya kwemukati . pa22 ° C ANT YAKABUDA UNGIRMI REMUMAI. Zvakawanda, zvidzidzo zvakarongeka zvinoongorora kukosha kungangoitika kwekugara pasi pehutongi hwekutamba kweTermforral Semuenzaniso, muzvidzidzo zvekufutisa, tsananguro yemubhadharo yerombo rinowanzove nekuda kwekuti iyo Murine Kurema Kwemhuka dzinowanzoitwa pamhuka dzine mwero dzakareredzwa pamhepo tembiricha nekuda kwekuwedzera kwee. Yakanyanyisa Kurema Kurasikirwa Kwemuviri Kwemunhu, kunyanya kana iyo Mechanism yechiitiko ichienderana nekuwedzera kweiyo bap, iyo inonyanya kushanda uye yakamisikidzwa tembiricha pane makumi matatu c.
Mukuwirirana neDanish Mhuka Yekuedza Mutemo (1987) uye National Institutes yehutano (Bhuku Repasiketi Nha. 85-23) Uye European Palace yekuchengetedza Vertebrate Yakashandiswa Kuedza uye Zvimwe ZveEurope. , 1985).
Makumi maviri nemana kupisa kwemakamuri. Male dio makonzo (mavhiki makumi maviri) akawanikwa kubva kumutengesi mumwechete uye akapihwa kushambadzira kune 40% yakakwira mafuta ekudya (Kwete. NJ, USA) uye mvura iri pasi pekurera mamiriro. Makonzo akagadziridzwa kune zvakasikwa pasvondo isati yatanga kudzidza. Mazuva maviri isati yatamisa kune zvisina kunanga calarimetry system, makonzo akaremerwa, akaiswa pasi peMRI Scanning (Echemritm, TX, USA) uye akaenzana nehuremu hwemuviri, mafuta uye akajairwa muviri.
Dhizaini yedhiramu yeiyo dhizaini inoratidzwa mumufananidzo 8 zviyero zvezviitiko nekuyera beam break. Xyz. Makonzo (n = 8) akaiswa mumwe nemumwe pa 22, 25, 27.5, kana makumi matatu ° C uchishandisa mubhedha uye nesting chiedza pa12: Chiedza chechiedza: Chiedza: 06: 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 00- 18:00) . 2500ml / min. Makonzo aive acclimatized kwemazuva manomwe asati anyoresa. Kurekodhwa kwakaunganidzwa mazuva mana mumutsara. Pashure pazvo, makonzo akachengetwa pakupisa kweechi 25, 27.5, uye 30 ° C kune imwe mazuva gumi nemaviri, mushure maizvozvo iyo sero makomendi yakawedzerwa sezvakatsanangurwa pazasi. Zvichakadaro, mapoka emakonzo anochengetwa pa 22 ° CVi akachengetwa pane ino tembiricha kwemazuva maviri (kuunganidza data hurefu), uye ipapo tembiricha yakawedzerwa mumatanho e2 ° C mamwe mazuva ese pakutanga kwechikamu chechiedza ( 06:00) Kusvikira Kusvika Kusvika 20. Mushure memamwe mazuva maviri ekuzvinyorera, c, matehwe akawedzerwa kumasero ese pakupisa kwese, uye kuunganidzwa kwedata kwakatanga pazuva repiri (zuva 17) uye kwemazuva matatu. Mushure meizvozvo (zuva 20), nesting zvinhu (8-10 g) yakawedzerwa kumasero ese pakutanga kwechiedza chechiedza (06:00) uye data yakaunganidzwa kwemamwe mazuva matatu. Nekudaro, pakupera kwechidzidzo ichi, makonzo akachengetwa paImba akachengetwa pakupisa uku kwemazuva makumi maviri nematanhatu uye pa 22 ° C kwemazuva masere apfuura, apo mbeva pane dzimwe tembiricha yakachengetwa pakupisa uku kwemazuva makumi matatu nemasere. / Mazuva makumi matatu nematatu. Makonzo akaiswa chikafu panguva yekudzidza.
Kurema kwakajairika uye dio makonzo akatevera maitiro akafanana ekudzidza. Pazuva -9, makonzo airemerwa, MRI akaongorora, uye akapatsanurana mumapoka akafanana nehuremu hwemuviri uye nekuumbwa kwemuviri. Pazuva -7, makonzo akaendeswa kune yakavharwa tembiricha inodzora zvisina kujairika calorimetry system yakagadzirwa neSyle Systems International (Nevada, USA). Makonzo akaiswa mumwe nemumwe aine pamubhedha asi pasina nesting kana pekugara zvinhu. Tembiricha yakaiswa kuna 22, 25, 27.5 kana 30 ° C. Mushure mevhiki imwe yeAcclimatization (mazuva -7 kusvika 0, mhuka dzainge dzisina kuvhiringidzwa), data yakaunganidzwa pamazuva mana akateedzana (mazuva 0-4, data rakaratidzwa mumaonde. 1, 2, 5). Pashure pazvo, makonzo akaitirwa 25, 27.5 uye 30 ° CVE yakachengetwa mumamiriro ezvinhu nguva dzose kusvika pazuva regumi nemana. Panguva imwecheteyo, tembiricha muboka ra2 22 ° C Boka rakawedzerwa panguva ye2 ° C zuva rega rega nekugadzirisa tembiricha (06:00 h) pakutanga kwechiedza (data inoratidzwa mu fig. 1) . Pazuva gumi nemashanu, tembiricha yakadonha kusvika ku22 ° C uye maviri mazuva e data yakaunganidzwa kuti ipe dataline data yekubhadhara kwakazotevera. Matehwe akawedzerwa kune ese makonzo pazuva 17, uye zvinhu nesting zvakawedzerwa pazuva 20 (Fig. 5). Pazuva regumi nemaviri, makonzo akaremerwa uye akaiswa pasi peMRI kutaridzika, uye akabva asiya ndega kwemaawa makumi maviri nemana. Musi wezuva makumi maviri nematatu, makonzo akafuratirwa kubva pakutanga kweiyo photaperiod (06:00) uye akagamuchira ogt (2 g / kg) na 12:00 (maawa matanhatu (6-7 maawa ekutsanya). Pashure pacho, mbeva yakadzoserwa kumatambudziko avo emarongero uye euthanized pazuva repiri (zuva 25).
Dio makonzo (n = 8) akateedzera iyo yakafanana protocol seyakajairika uremu makonzo (sezvakatsanangurwa pamusoro uye mumufananidzo 8). Makonzo akachengetwa 45% HFD yose masimba ekutsvaga mari yekuedza.
VO2 uye VCO2, pamwe chete nemvura yemvura kumanikidzwa kwemvura, zvakanyorwa panguva yekuwedzera kwe1 Hz ine nguva yenguva dzose ye2,5 min. Chikafu uye kudya kwemvura kwakaunganidzwa nekuenderera mberi kurekodha (1 hz) yehuremu hwezvikafu nemvura. Mhando yemhando yakashandiswa yakataura resolution ye 0.002 g. Zviitiko zvezviitiko zvakanyorwa uchishandisa 3D XYZ BEAM Array Monitor, data yakaunganidzwa kugadziriswa kwemukati yegumi nenhatu kuti iwane nzvimbo yakafamba (m) ine spatial resolution ye 0.25 cm. Iyo data yakagadziriswa ine systems masisitimu macro muturikiri v.2.41, kuverenga ee uye rer uye kuseya kunze kwekunze (yechiitiko choupfu. Muturikiri weMacro anogadziriswa kuti abudise data kune ese ma parameter maminitsi mashanu.
Pamusoro pekudzora ee, tembiricha tembiricha inogona zvakare kudzora zvimwe zvikamu zve metabolism, kusanganisira postplandial glucese metabolism, nekudzora chinyorwa cheGlucose-metabolizing mahormone. Kuedza iyi hypothesis, takapedzisira tapedza tembiricha tembiricha nekumutsidzira yakajairika uremu makonzo ne dio aral glucose mutoro (2 g / kg). Nzira dzinotsanangurwa zvakadzama mune zvimwe zvinhu zvekuwedzera.
Pakupera kwekudzidza (zuva 25), makonzo akafuratirwa kwemaawa 2-3 (kutanga pa03:00), anesthetised neIsomlurane, uye yakazara yakazara neRetroorbital Venipuncture. Kurehwa kwePlasma Lipids neHormone uye LIPIDS Mune Chikara Chinotsanangurwa muzvishandiso zvekuwedzera.
Kuti uongorore kuti denderedzwa tembiricha inokonzeresa shanduko yedanho muLiposes inokanganisa Lipolysis, Inguinal uye Epidiynal Adonline Tisue yakafemerwa zvakananga kubva pamakonzo mushure mechikamu chekupedzisira chekubuda ropa. Tishu yakagadziriswa uchishandisa iyo ichangobva kugadzirwa ex Vivo Lipolysis assay inotsanangurwa nenzira dzekuwedzera.
Brown Adonline Tishu (Bat) yakaunganidzwa pazuva rekupera kwekudzidza uye kugadziriswa sekutsanangurwa kwenzira dzekuwedzera.
Dhata inoburitswa seye zvinoreva ± SEM. Girafu dzakagadzirwa muGraphpad Prism 9 (La Jolla, CA) uye mifananidzo yakagadziriswa muAdobe Itart (Systems Systems Yakabatanidzwa, San Jose, CA). Statistical kukosha kwakaongororwa muGraphpad Prism uye yakaedzwa neyekupedzisira t-bvunzo Iyo Gaussian kugoverwa kweiyo data yakasimbiswa neiyo D'Agostino-pearson yakajairika bvunzo usati waedza. Saizi yemuenzaniso inoratidzwa muchikamu chinoenderana che "mhinduro", pamwe nengano. Kudzokorora kunotsanangurwa sechiyero chero chiyero chakatorwa pane imwe mhuka (mu vivo kana pane tishu sampuli). Panyaya yekubereka data, mubatanidzwa pakati pekushandiswa kwesimba uye kesi yekudziya yakaratidza muzvidzidzo zvina zvakazvimiririra uchishandisa mikonzo akasiyana neyekudzidza kwakafanana.
Yakadzama protocols, midziyo, uye data rakabikwa rinowanikwa pane chikumbiro chakaringana kubva kune mutungamiri munyori rune E. kuhre. Iyi fundo haina kuumba matsva akasiyana marekodhi, transgenic mhuka / mitezo yemitsetse, kana kutevedzana data.
Kuti uwane rumwe ruzivo nezve dhizaini yekudzidza, ona iyo yakasikwa yekutsvaga chirevo ichibatanidza yakabatana nenyaya ino.
Yese data fomu fomu girafu. 1-7 yakaiswa muSainzi Database repository, nhamba yekuwana: 1253.1.Scienceb.02284 kana https: 1252284 kana https: 1253284. Iyo data inoratidzwa muEsm inogona kutumirwa kunomhanya e kuhre mushure mekuedzwa zvine musoro.
Nilsson, C., Run, K., Yan, FF, Larsen, MO & Tang-Chritensen, M. Laboratory mhuka dzedzidzo yekufutisa. Nilsson, C., Run, K., Yan, FF, Larsen, MO & Tang-Chritensen, M. Laboratory mhuka dzedzidzo yekufutisa.Nilsson k, Run K, Yang FF, Larsen Mo. Uye Tang-Chrateensen M. Laboratory mhuka seSurrogate mhando dzekufutisa kwevanhu. Nilsson, C., Run, K., Yan, FF, Larsen, MO & Tang-Chrenderenen, M. 实验动物作为人类肥胖的替代模型. Nilsson, C., Run, K., Yan, FF, Larsen, MO & Tang-Christensen, M. Mhuka dzinoedza semuenzaniso wekutsiva vanhu.Nilsson k, Run K, Yang FF, Larsen Mo. Uye Tang-Christenen M. Laboratory mhuka seSurrogate mhando dzekufutisa muvanhu.Acta Pharmacology. Mhosva 33, 173-181 (2012).
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Kutumira Nguva: Oct-28-2022
